Anas Alawawdeh1, Cynthia Piantadosi2, Amanda Rose Townsend1, Christos Stelios Karapetis3, Rob Padbury2, Amitesh Chandra Roy3, James Moore4, Guy Maddern5,6, David Roder7, Annabelle Smith1, Timothy Jay Price8,9. 1. Department of Medical Oncology, The Queen Elizabeth Hospital and University of Adelaide, Adelaide, SA, Australia. 2. Division of Surgery, Flinders Medical Centre, Adelaide, SA, Australia. 3. Department of Medical Oncology, Flinders Medical Centre and Flinders University, Adelaide, SA, Australia. 4. Department of Surgery, Royal Adelaide Hospital, Adelaide, SA, Australia. 5. Department of Surgery, The Queen Elizabeth Hospital, Adelaide, SA, Australia. 6. Discipline of Surgery, University of Adelaide, Adelaide, SA, Australia. 7. Sansom Institute for Health Research, Adelaide, SA, Australia. 8. Department of Medical Oncology, The Queen Elizabeth Hospital and University of Adelaide, Adelaide, SA, Australia. Timothy.Price@sa.gov.au. 9. TQEH, 28 Woodville Road, Woodville, SA, 5011, Australia. Timothy.Price@sa.gov.au.
Abstract
BACKGROUND: Effective targeting of RAS mutations has proven elusive until recently. Novel agents directly targeting KRAS G12C have shown promise in early-phase clinical trials that included patients with metastatic colorectal cancer. Prior reports have suggested that G12C mutation may be predictive of poor outcome. OBJECTIVE: Assessment of the specific characteristics and prognostic implications of individual RAS mutation subtypes in patients with metastatic colorectal cancer. PATIENTS AND METHODS: Retrospective review of individual RAS mutation types from the South Australian Metastatic Colorectal Registry between 2006 and 2020. RESULTS: Of the 5165 patients entered onto the registry, 2305 (45%) had RAS mutation results available. 772 (33%) had a RAS mutation. The nature of the RAS mutation was available in 668 (87% of those with RAS mutation). Rare mutations (outside codons 12 and 13) made up 12.6% of the total. There were numerical differences in survival between the specific RAS mutation subgroups, with the longest median overall survival (30 months) observed in those with G12S mutations. However, there was no statistical difference in survival when comparing the various RAS mutations, including the comparison of G12C to G12S (p = 0.38). Patients with cancer harbouring rare RAS mutations had a median survival of 30 months. CONCLUSIONS: Whilst the G12S mutation was associated with the longest survival numerically, the observed survival for patients with the most common RAS mutations (G12C, G12V, G12A, G12D and G13D) did not significantly differ.
BACKGROUND: Effective targeting of RAS mutations has proven elusive until recently. Novel agents directly targeting KRAS G12C have shown promise in early-phase clinical trials that included patients with metastatic colorectal cancer. Prior reports have suggested that G12C mutation may be predictive of poor outcome. OBJECTIVE: Assessment of the specific characteristics and prognostic implications of individual RAS mutation subtypes in patients with metastatic colorectal cancer. PATIENTS AND METHODS: Retrospective review of individual RAS mutation types from the South Australian Metastatic Colorectal Registry between 2006 and 2020. RESULTS: Of the 5165 patients entered onto the registry, 2305 (45%) had RAS mutation results available. 772 (33%) had a RAS mutation. The nature of the RAS mutation was available in 668 (87% of those with RAS mutation). Rare mutations (outside codons 12 and 13) made up 12.6% of the total. There were numerical differences in survival between the specific RAS mutation subgroups, with the longest median overall survival (30 months) observed in those with G12S mutations. However, there was no statistical difference in survival when comparing the various RAS mutations, including the comparison of G12C to G12S (p = 0.38). Patients with cancer harbouring rare RAS mutations had a median survival of 30 months. CONCLUSIONS: Whilst the G12S mutation was associated with the longest survival numerically, the observed survival for patients with the most common RAS mutations (G12C, G12V, G12A, G12D and G13D) did not significantly differ.